Methyl Jasmonate Protects Microglial Cells Against β-Amyloid-Induced Oxidative Stress and Inflammation via Nrf2-Dependent HO-I Pathway

Background: beta-Amyloid (A beta) induces oxidative stress and inflammation of microglial cells, thus leading to Alzheimer's disease. Methyl jasmonate (MeJA) is reported to have anti-inflammatory and anti-oxidant effects. However, the potential roles of MeJA in A beta-induced cell activities and the underlying mechanism are unclear. Methods: Microglial cell line BV-2 was stimulated by 20 mu M A beta and/or 20 mu M MeJA and then divided into four groups (control, A beta, MeJA, and A beta+MeJA). Cell viability was detected by MTT assay. MDA, SOD activity, and ROS were detected by fluorescence spectrophotometry and immunofluorescence assay. Nrf2 and HO-1 were detected by qRT-PCR and Western blot. Furthermore, inflammatory cytokines (p-NF kappa B, TLR4, TNF-alpha, IL-1 beta, and IL-6) and apoptosis factors (Bcl-2, Bax, and cl-casp-3) were detected by Western blot. TUNEL assay was applied to investigate apoptosis rate. Moreover, the mechanism of how MeJA played anti-oxidative stress and anti-inflammatory roles was investigated by silencing of Nrf2 via siRNA. Results: The result of MTT assay showed that MeJA improved the decreased viability of BV-2 cells induced by A beta. The detection of MDA, SOD activity, and ROS showed the oxidative stress levels were decreased in A beta+MeJA group compared with A beta group. Nrf2, HO-1, and SOD were significantly up-regulated in A beta+MeJA group compared with A beta group (p<0.01). In contrast, inflammatory cytokines were significantly down-regulated in A beta+MeJA group compared with A beta group (p<0.05). Similarly, the expressions of apoptosis cytokines and TUNEL assay suggested a decreased apoptosis rate in A beta+MeJA group compared to A beta group (p<0.01). Finally, results of Nrf2 knockdown experiment showed down-regulations of anti-oxidative stress factors (Nrf2, HO-1 and SOD), up-regulations of inflammatory cytokines, and increased ratio of Bax to Bcl in A beta+MeJA+si-Nrf2 group compared with A beta+MeJA group (p<0.01). Conclusion: MeJA could relieve A beta-induced oxidative stress and inflammatory response in microglial cells by activating Nrf2/HO-1 pathway.